The invention relates to a method and the associated apparatus for performing intramyocardiac therapeutic treatment by means of the controlled infusion, in this anatomical location, of therapeutic fluids of varying nature and composition. With this method and apparatus it is possible to treat patients who suffer from cardiac ischaemia and who are not able to tolerate surgical therapy involving a coronary bypass or coronary angioplasty using catheters. At present there are many patients suffering from heart disease which is advanced to the point where it can no longer be treated using the solutions mentioned. Complete re-vascularization is not possible in 20% of the patients who undergo bypass surgery. The patients who cannot be treated with the abovementioned solutions belong, for example, to the following categories: patients with extensive heart disease affecting the distal vessels; patients with symptomatic ischaemia resulting from a diseased vessel which is too small to be bypassed; patients who do not have adequate ducts for bypassing; patients with total chronic occlusion and with distal vessels which are small and/or cannot be viewed.
A new therapy which is currently becoming more widespread for the treatment of this type of patient consists in the percutaneous injection, into the cardiac muscle, of genic substances, for example DNA plasmids, which induce the formation of new blood vessels. At least six different carrier systems have been used for genic transfer to the heart muscle cells, namely: DNA devoid of viral or physical adjuvants which increase the genic release; DNA encapsulated in modified liposomes; DNA complexed with cationic liposomes; retroviral carriers; adeno-associated viral carriers. This therapy is currently performed by making a small incision in the chest in order to inject the abovementioned plasmids into the myocardium, continuously monitoring the patient by means of transoesophageal echocardiography in order to check the movement of the cardiac wall during the percutaneous injection, in order to prevent the plasmid being injected into the blood, inside the cavity of the left-hand ventricle. The recent clinical experiments involving injection of plasmids into the myocardium, during surgical treatment or a mini-thoracotomy, are very interesting, but are unable to solve many problems when this procedure is used as the one and only therapy, in particular problems relating to optimization of the most suitable site for injection and the number and dosing of the intramyocardial injections. It is also obvious that the surgical solution limits very much the possibility of performing multiple treatment or treatment which is repeated over time.
It was thought that a catheter system suitable for the intramyocardiac injection of plasmids may be able to overcome the limitations of the present surgical solution indicated above.
According to the publication xe2x80x9cPercutaneous Transluminal Gene Transfer into Canine Myocardium in Vivo by Replication-Defective Adenovirusxe2x80x9d Jian Jun Li et. al. (Cardiovascular Research 1995: 30: 97-105), previous experiments involving the percutaneous injection of genes into the myocardium of dogs, by means of adenovirus, were performed using an injection catheter composed of a catheter guide and a guided catheter, with a needle at its terminal end, inserted into the left-hand ventricle of the heart. Under a fluoroscope, the needle was inserted into the myocardium and its correct position of insertion was confirmed by suction of the blood. If the needle is inserted into the wall of the cardiac muscle, its lumen is closed by the muscle itself and therefore the suction of blood is prevented.
Various injection catheters have been studied in order to improve the injection of a drug into an area inside the human body. Injection catheters have for example been produced by Wilson Cook Medical Inc. (Cook Italia Sri), said catheters being specifically designed for the sclerotherapeutic endoscopic treatment of oesophageal varices. The Boston Scientific Corporation markets needles for liquid injection therapy using a dedicated twin-lumen catheter and associated extendable and retractable needle with an ample washing lumen for ensuring vision with an endoscope in bleeding conditions.
None of the catheters with injection needles proposed by the current technology has been specifically developed and can neither be adapted to solve the problem of percutaneous and transvascular injection of plasmids into the human myocardium. With a needle catheter of the known type it is difficult to maintain a fixed position inside the moving wall of the myocardium and it is therefore difficult to inject, in a reliable manner, plasmids into the said wall. Similar difficulties have been encountered with the catheters of pacemakers when they have to be positioned in a different point of the apex of the right-hand ventricle, for example in the interatrial or interventricular septum. In these cases, a helical electrode screwed into the wall of the endocardium, in order to ensure immediate stability of the implant pending the growth of tissue thereon, is used. The use of a helical and hollow electrode for the injection of liquids into the human body has been described in U.S. Pat. No. 5,431,649 for a purpose different from that of the present invention, namely for the hyperthermic treatment of neoplasia of the prostate and for treatment of myocardiac ablation by means of radiofrequency, using a perfusion of saline solution through the cavity of the helical electrode.
An important factor which prevents the use of the abovementioned catheter perfusion systems for the function in question is the fact that they are not able to provide a safe, reproducible and recordable method for demonstrating that the injection of the plasmids is performed in a selected area of the myocardium and not in the blood stream; in fact the aforementioned solution of confirming the position of the needle by suction is not suitable for this purpose on account of the high risk of false situations created by the closure of the needle lumen by blood clots.
A recent publication xe2x80x9cTranscatheter Subendocardial Infusion. A Novel Technique for Mapping and Ablation of Ventricular Myocardiumxe2x80x9d, Andreas Goette et. al. (Circulation 1996: 94: 1149-1455) described an infusion catheter equipped with an electrode corresponding to the injection needle located on the distal end of said catheter and provided with a second ring electrode in the vicinity of the same needle. Two lumina which are formed inside the catheter and by means of which it is possible to perform a sequential administration of fluid mixtures converge towards this needle. A tracer substance is injected via a lumen of the catheter in order to map, by means of fluoroscopy, the point of injection of the needle into the myocardium of the left-hand ventricle, while a fluid mixture with ethanol is subsequently injected through the second lumen of the catheter in order to perform a chemical ablation of a volume of the myocardium. By means of this method, with the associated catheter, it is possible to identify with reasonable certainty the area of the myocardium into which the needle is inserted, but the problems, as described in the abovementioned publication, resulting from the difficulty of keeping a straight needle in the correct position in a beating myocardium and preventing remixing between the fluids introduced through the two catheter lumina, the latter intercommunicating via the common lumen of the injection needle, cannot be solved. Owing to the inherent elasticity of the material from which the lumina of the catheter may be made and the notable curvature to which the catheter itself is subject during insertion into the human body, it cannot be ruled out that the pressure exerted on a fluid which is to be injected may cause a partial transfer of this fluid from its lumen under pressure to the other lumen which is at a lower pressure, with the result of unexpected and constant mixing of the two fluids and possible limitation of the volume of the fluid actually injected into the myocardium, since a part of this fluid, instead of being discharged from the needle, flows back into the lumen of the catheter which is at a pressure less than that of the active lumen.
U.S. Pat. No. 5,354,279 (xe2x80x9cPlural Needle Injection Catheterxe2x80x9d) envisages a catheter provided at its terminal end with a plurality of thin pre-formed metal needles emerging in a ray-like arrangement and designed to release pharmaceutical substances onto the arteries. The lumina of these needles communicate, however, with a single lumen of the catheter so that this apparatus may not be used for the purposes of the present invention, either.
By way of conclusion, the known art, with the procedures and the devices described based on a catheter system with injection needle, does not allow the practical realization of an apparatus and a method for injecting plasmids solely using the intramyocardiac method, owing to problems associated with the movement of the endocardium and the impossibility of separating completely injection of the therapeutic fluids from injection of the tracer fluid.
The object of the invention is to solve these and other problems of the already known art by means of a catheter provided with two or more longitudinal lumina and provided at its terminal end with a multilumen needle system, each lumen of this needle system having its own discharge opening and being connected to a corresponding lumen of the catheter. The lumina of the catheter are connected to external systems for releasing separately tracer fluids for external image diagnostics systems by means of which it is possible to verify the correct position of the needle in the cardium tissue and release therapeutic fluids, for example DNA plasmids. The needle system in question may be formed by a multilumen needle or by several single-lumen needles arranged alongside each other and each connected to a corresponding lumen of the catheter.